PROJECT SUMMARY To see well, the cornea must maintain near perfect clarity and shape. Several disease processes can distort corneal shape and degrade vision. These include ectasia/keratoconus (stromal thinning and bulging), primary epithelial deformation (contact lens-related warpage, dry eye, epithelial basement membrane dystrophy), and stromal changes (scar, stromal dystrophy, surgery). Some of these conditions can appear similar on standard anterior topography and yet require very different treatments. Therefore a goal of this project is to use optical coherence tomography (OCT), a 3-dimensional imaging technology with micrometer-level resolution, to differentiate between different types of corneal shape irregularities. The unique ability of OCT to measure epithelial thickness and posterior topography will be used to develop new metrics for staging and monitoring of ectasia and primary epithelial deformation. We will also improve the treatment of corneal stromal irregularities by combining OCT planning and topography-guided excimer laser ablation, which has only recently become available in the U.S. Our overall goal is to improve the early detection, differential diagnosis, staging, monitoring, and treatment of irregular corneas by using advanced optical imaging and laser technologies to achieve the following Specific Aims: (1) Develop an OCT-based system to classify and evaluate corneal shape irregularities. Standard corneal topography only measures the anterior corneal surface and cannot by itself differentiate between different causes of irregularities. In a cross-sectional clinical study, we will develop mathematical analyses of OCT maps of corneal anterior and posterior topography, epithelium, and pachymetry to improve the early detection, classification, and staging of irregularities including ectasia, epithelial deformations, and stromal changes. (2) Develop OCT metrics for more sensitive detection of keratoconus progression. Standard anterior topographic parameters such as maximum keratometry have poor reproducibility and poor detection sensitivity in early disease. Our preliminary results show that OCT epithelial and posterior topographic measurements are more sensitive to early keratoconus and have better repeatability. This could enable more timely identification of patients who need collagen crosslinking to stabilize the cornea. Early detection of progression will be tested in a longitudinal study of patients with subclinical keratoconus. (3) Develop OCT-and-topography guided phototherapeutic keratectomy (PTK) for irregular corneas. We have demonstrated that transepithelial PTK with OCT planning can significantly improve vision for patients with scarred or irregular corneas. We propose to further improve operative results using the newly available topography-guided excimer laser, which has been approved for laser-assisted in situ keratomileusis (LASIK) in normal eyes but has not yet been tested in PTK. We plan to conduct a clinical trial of OCT-and-topography guided PTK for patients with corneal scars, stromal dystrophies, and other irregularities.